Category: 399-76-8

Bowroju, Suresh K.; Mainali, Nirjal; Ayyadevara, Srinivas; Penthala, Narsimha R.; Krishnamachari, Sesha; Kakraba, Samuel; Reis, Robert J. Shmookler; Crooks, Peter A. published the artcile< Design and synthesis of novel hybrid 8-hydroxy quinoline-indole derivatives as inhibitors of Aβ self-aggregation and metal chelation-induced Aβ aggregation>, Electric Literature of 399-76-8, the main research area is hydroxyquinoline indole quinoline indolylpiperazine preparation amyloid beta42 aggregation neurotoxicity; Alzheimer’s disease; Aβ-aggregation; clioquinol analogues; hybrid 8-hydroxyquinoline-indole analogs; metal chelating agents.

A series of novel hybrid 8-hydroxyquinoline-indole derivatives I (X = H, Cl; R = H, OMe, F), II (R = H, OMe), III (X = H, Cl, Br; R = H, OMe, F) were synthesized and screened for inhibitory activity against self-induced and metal-ion induced Aβ1-42 aggregation as potential treatments for Alzheimer’s disease (AD). In vitro studies identified the most inhibitory compounds against self-induced Aβ1-42 aggregation as III (X = Cl; R = H), III (X = H; R = OMe) and III (X = Cl; R = OMe) (EC50 = 1.72, 1.48 and 1.08μM, resp.) compared to the known anti-amyloid drug, clioquinol (EC50 = 9.95μM). The fluorescence of thioflavin T-stained amyloid formed by Aβ1-42 aggregation in the presence of Cu2+ or Zn2+ ions was also dramatically decreased by treatment with III (X = H, Cl; R = H, OMe). The most potent hybrid III (X = Cl; R = OMe) afforded 82.3% and 88.3% inhibition, resp., against Cu2+- induced and Zn2+- induced Aβ1-42 aggregation. Compounds III (X = H, Cl; R = H, OMe) were shown to be effective in reducing protein aggregation in HEK-tau and SY5Y-APPSw cells. Mol. docking studies with the most active compounds performed against Aβ1-42 peptide indicated that the potent inhibitory activity of compounds III (X = H, Cl; R = OMe) were predicted to be due to hydrogen bonding interactions, π-π stacking interactions and π-cation interactions with Aβ1-42, which may inhibit both self-aggregation as well as metal ion binding to Aβ1-42 to favor the inhibition of Aβ1-42 aggregation.

Molecules published new progress about Alzheimer disease. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Electric Literature of 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wang, Youde; Yan, Zhiwei; Guo, Yachun; Zhang, Liying published the artcile< Discovery and evaluation of novel benzazepinone derivatives as glycogen phosphorylase inhibitors with potent activity>, Recommanded Product: 5-Fluoroindole-2-carboxylic acid, the main research area is benzazepinone derivative glycogen phosphorylase inhibitor hyperglycemia; benzazepinone derivatives; biological activity; glycogen phosphorylase inhibitors; molecular docking; type 2 diabetes.

Glycogen phosphorylase (GP) is a key enzyme of glycogen catabolism, so it is significant to discover a new GP inhibitor. A series of benzazepinone derivatives were discovered as GP inhibitors with potent activity. Among these derivatives, compound 5d showed significant potential against rabbit muscle GPa (IC50 = 0.25 ± 0.05 μM) and cellular efficacy. The in vivo study revealed that 5d significantly inhibited increases in fasting blood glucose level in two kinds of hyperglycemic mice models. The possible binding mode of compound 5d was explored based on mol. docking simulations. These results indicated that derivatives with benzazepinone were potential chem. entities against hyperglycemia.

Future Medicinal Chemistry published new progress about Absorption. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Recommanded Product: 5-Fluoroindole-2-carboxylic acid.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Nerella, Ashok; Jeripothula, Madhukar published the artcile< Design, synthesis and biological evaluation of novel deoxyvasicinone-indole as multi-target agents for Alzheimer's disease>, Synthetic Route of 399-76-8, the main research area is oxo tetrahydropyrroloquinazolinyl heteroaryl carboxamide preparation cholinesterase inhibitor mol docking; Acetylcholinesterase inhibitors; Alzheimer’s disease; Deoxyvasicinone; Indole; Multi target agents.

A series of multifunctional hybrids I [R = 1H-indol-2-yl, 1-benzofuran-2-yl, 1-benzothiophen-2-yl, etc.; R1 = H, Me] against Alzheimer’s disease were designed and obtained by conjugating the pharmacophores of deoxyvasicinone and indole. These analogs of deoxyvasicinone-indole were evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and as inhibitors of amyloid aggregation (Aβ1-42) for treatment of Alzheimer’s disease (AD). Subsequently, AChE induced Aβ aggregation inhibition test was also performed for selected compounds Biol. activity results demonstrated that compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] was the most potent and balanced dual ChEs inhibitor with IC50 values 0.12μM and 0.15μM for eeAChE and eqBuChE, resp. Kinetic anal. and docking study indicated that compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] was a mixed-type inhibitor for both AChE and BuChE. Compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] also found to be the best inhibitors of self-induced Aβ1-42 aggregation with IC50 values of 1.21μM. Compound I [R = 5-methoxy-1H-indol-2-yl, R1 = H] also afforded excellent inhibition of AChE-induced Aβ1-42 aggregation by 81.1%. Overall, these results indicate that I [R = 5-methoxy-1H-indol-2-yl, R1 = H] may be considered as lead compound for the development of highly effective anti-AD drugs.

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Synthetic Route of 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sreenivasa Rao, Ramana; Shajan, Femil Joseph; Reddy, D. Srinivasa published the artcile< A route to access imidazol[1,5-a]indole-1,3-diones and pyrrolo[1,2-c]imidazole-1,3-diones>, Electric Literature of 399-76-8, the main research area is imidazolindoledione pyrroloimidazoledione preparation; indole pyrrole carboxylic acid aniline carbonyldiimidazole microwave irradiation.

A novel and practical route to synthesize imidazol[1,5-a]indoles I (R = 3,5-Cl, 4-OCF3, 4-iPr, etc.) and pyrrolo[1,2-c]imidazoles via N-H functionalization has been developed. Indole-2-carboxylic acid or pyrrole-2-carboxylic acid with diverse aniline groups and carbonyldiimidazole (CDI), in the presence of a base under microwave conditions, resulted in imidazol[1,5-a]indoles and pyrrolo[1,2-c]imidazoles, resp. The present method is free of work-up and no need for column chromatog. Both title scaffolds can serve as useful heterocyclic scaffolds in medicinal chem. as such, or they can be used as building blocks to construct different classes of useful compounds

Organic & Biomolecular Chemistry published new progress about Anilines Role: RCT (Reactant), RACT (Reactant or Reagent). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Electric Literature of 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Oderinde, Martins S.; Ramirez, Antonio; Dhar, T. G. Murali; Cornelius, Lyndon A. M.; Jorge, Christine; Aulakh, Darpandeep; Sandhu, Bhupinder; Pawluczyk, Joseph; Sarjeant, Amy A.; Meanwell, Nicholas A.; Mathur, Arvind; Kempson, James published the artcile< Photocatalytic Dearomative Intermolecular [2 + 2] Cycloaddition of Heterocycles for Building Molecular Complexity>, HPLC of Formula: 399-76-8, the main research area is regioselective diastereoselective photocatalytic dearomative intermol cycloaddition indole alkene.

Indole and indoline rings are important pharmacophoric scaffolds found in marketed drugs, agrochems., and biol. active mols. The [2 + 2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp3-rich cyclobutane-fused scaffolds with potential applications in drug discovery programs. A general platform for visible-light mediated intermol. [2 + 2] cycloaddition of indoles with alkenes has been realized. A substrate-based screening approach led to the discovery of tert-butyloxycarbonyl (Boc)-protected indole-2-carboxyesters as suitable motifs for the intermol. [2 + 2] cycloaddition reaction. Significantly, the reaction proceeds in good yield with a wide variety of both activated and unactivated alkenes, including those containing free amines and alcs., and the transformation exhibits excellent regio- and diastereoselectivity. Moreover, the scope of the indole substrate is very broad, extending to previously unexplored azaindole heterocycles that collectively afford fused cyclobutane containing scaffolds that offer unique properties with functional handles and vectors suitable for further derivatization. DFT computational studies provide insights into the mechanism of this [2 + 2] cycloaddition, which is initiated by a triplet-triplet energy transfer process. The photocatalytic reaction was successfully performed on a 100 g scale to provide the dihydroindole analog.

Journal of Organic Chemistry published new progress about [2+2] Photocycloaddition reaction (diastereo/regioselective). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, HPLC of Formula: 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Rassi, Somayeh; Baharfar, Robabeh published the artcile< Synthesis of indole based amides using immobilized lipase on graphene oxide (GO@lipase) as a retrievable heterogeneous nano biocatalyst>, SDS of cas: 399-76-8, the main research area is lipase immobilized graphene oxide catalyst preparation thermal stability; indolyl carboxylic acid benzaldehyde alkyl isocyanide lipase Passerini reaction; phenyl alkylamino oxoethyl indolyl carboxylate preparation green chem.

A green and efficient one-pot procedure to achieved indole based amides using Passerini reaction involving indole-2-carboxylic acids, benzaldehydes and alkyl isocyanides in the presence of immobilized lipase on graphene oxide as a heterogeneous nano biocatalyst was developed. This method has the advantages of simple operation, mild reaction conditions and good to excellent yields. The features of this method are highlighted by using a retrievable nanostructure catalyst. This process was asserted to be efficient in the synthesis of indole derivatives

Polyhedron published new progress about Amides Role: BPN (Biosynthetic Preparation), BIOL (Biological Study), PREP (Preparation). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, SDS of cas: 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sawama, Yoshinari; Nakano, Akihiro; Matsuda, Takumi; Kawajiri, Takahiro; Yamada, Tsuyoshi; Sajiki, Hironao published the artcile< H-D Exchange Deuteration of Arenes at Room Temperature>, Recommanded Product: 5-Fluoroindole-2-carboxylic acid, the main research area is deuterated arene chemoselective preparation; platinum iridium catalyst deuteration arene deuterium oxide under argon.

Arenes underwent C-H deuteration reactions with D2O in the presence of Pt/C, Ir/C, or combinations of both catalysts in isopropanol/D2O under argon at ambient temperature to yield arenes deuterated at the arene C-H bonds.

Organic Process Research & Development published new progress about Aromatic hydrocarbons Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Recommanded Product: 5-Fluoroindole-2-carboxylic acid.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wang, Lei; Fang, Kun; Cheng, Junfei; Li, Yu; Huang, Yahui; Chen, Shuqiang; Dong, Guoqiang; Wu, Shanchao; Sheng, Chunquan published the artcile< Scaffold Hopping of Natural Product Evodiamine: Discovery of a Novel Antitumor Scaffold with Excellent Potency against Colon Cancer>, Application In Synthesis of 399-76-8, the main research area is colon cancer antitumor agents SAR topoisomerase tubulin scaffold apoptosis.

Inspired by the natural product evodiamine, a novel antitumor indolopyrazinoquinazolinone scaffold was designed by scaffold hopping. Structure-activity relationship studies led to the discovery of compound 15j, which shows low nanomolar inhibitory activity against the HCT116 cell line. Further antitumor mechanism studies indicated that compound 15j acted by the dual inhibition of topoisomerase 1 and tubulin and induced apoptosis with G2 cell-cycle arrest. The quaternary ammonium salt of compound 15j (compound 15js) exhibited excellent in vivo antitumor activity (TGI = 66.6%) in the HCT116 xenograft model with low toxicity. Indolopyrazinoquinazolinone derivatives represent promising multitargeting antitumor leads for the development of novel antitumor agents.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Application In Synthesis of 399-76-8.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Yu, Hui-juan; Zhao, Wei; Xie, Mengting; Li, Xiaoqing; Sun, Ming; He, Jun; Wang, Lu; Yu, Lin published the artcile< Real-Time Monitoring of Self-Aggregation of β-Amyloid by a Fluorescent Probe Based on Ruthenium Complex>, Formula: C9H6FNO2, the main research area is self aggregation beta amyloid ruthenium complex fluorescent imaging.

Self-accumulation of amyloid-β protein (Aβ) into insoluble fibrils is the major hallmark of Alzheimer’s disease. Real-time monitoring of fibril growth is essential for clarifying the mechanism underlying aggregation and discovering therapeutic targets. A variety of approaches including NMR, electron microscopy (EM), at. force microscopy (AFM), and total internal reflection fluorescence microscopy (TIRFM) have been explored to monitor the fibril growth or reveal morphol. of Aβ aggregates. However, none of the methods allow real-time observation under physiol. conditions while without any perturbations. Here, the authors present a fluorescent probe [Ru(phen)2(fipc)]2+ (Ru-fipc) (phen = 1,10-phenanthroline, fipc = 5-fluoro-N-(1,10-phenanthrolin-5-yl)-1H-indole-2-carboxamide) that can bind to all the Aβ forms, i.e., monomers, oligomers, and fibrils, while not perturbing aggregation. Using this probe in combination with laser confocal microscopy, the entire aggregation process could be clearly and exactly imaged at the single fibril level. The reliability of Ru-fipc was confirmed based on colocalization with thioflavin T (ThT). Importantly, Ru-fipc can be used to monitor the very early nucleation and oligomerization process, which is thought to be a critical step in the development of neurotoxicity while it cannot be visualized with ThT. To the knowledge, this is the first fluorescent probe developed for real-time monitoring of Aβ aggregation, especially for the very early assembly stage, in solution with minimal perturbation. This method is suitable for in vitro and in vivo studies. The authors believe this would provide a valuable complementary tool for the study of pathogenesis and discovery of therapeutic targets of neurodegenerative diseases.

Analytical Chemistry (Washington, DC, United States) published new progress about Confocal laser scanning microscopy. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Formula: C9H6FNO2.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Avula, Sreenivas; Peng, Xudan; Lang, Xingfen; Tortorella, Micky; Josselin, Beatrice; Bach, Stephane; Bourg, Stephane; Bonnet, Pascal; Buron, Frederic; Ruchaud, Sandrine; Routier, Sylvain; Neagoie, Cleopatra published the artcile< Design and biological evaluation of substituted 5,7-dihydro-6H-indolo[2,3-c]quinolin-6-one as novel selective Haspin inhibitors>, Category: indole-building-block, the main research area is dihydroindoloquinolinone preparation; protein kinase haspin inhibition SAR antitumor cytotoxicity mol docking; Haspin kinase; Indoloquinoline; cell viability; docking.

A library of substituted indolo[2,3-c]quinolone-6-ones was developed as simplified Lamellarin isosters. Synthesis was achieved from indole after a four-step pathway sequence involving iodination, a Suzuki-Miyaura cross-coupling reaction and a reduction/lactamization sequence. The inhibitory activity of the 20 novel derivatives was assessed on Haspin kinase. Two of them possessed an IC50 of 1 and 2 nM with selectivity towards a panel of 10 other kinases including the parent kinases DYRK1A and CLK1. The most selective compound exerted addnl. a very interesting cell effect on the osteosarcoma U-2 OS cell line.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 399-76-8 belongs to class indole-building-block, and the molecular formula is C9H6FNO2, Category: indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles